Trial Outcomes & Findings for A Study of Oral Valcyte (Valganciclovir) in Pediatric Kidney Transplant Recipients (NCT NCT01376804)
NCT ID: NCT01376804
Last Updated: 2017-07-11
Results Overview
An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. Pre-existing conditions which worsen during a study were reported as AEs. A SAE was any experience that: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically significant.
COMPLETED
PHASE4
57 participants
52 weeks
2017-07-11
Participant Flow
Participant milestones
| Measure |
Valganciclovir
Participants received a once daily oral dose (solution or tablets) of valganciclovir starting within 10 days of kidney transplant for up to 200 days post-transplant. Dose \[in milligrams (mg)\] was calculated using the algorithm \[7 \* Body Surface Area \* Creatinine Clearance\].
|
|---|---|
|
Treatment Period
STARTED
|
57
|
|
Treatment Period
Received Study Drug
|
56
|
|
Treatment Period
COMPLETED
|
49
|
|
Treatment Period
NOT COMPLETED
|
8
|
|
Follow-up Period
STARTED
|
55
|
|
Follow-up Period
COMPLETED
|
55
|
|
Follow-up Period
NOT COMPLETED
|
0
|
Reasons for withdrawal
| Measure |
Valganciclovir
Participants received a once daily oral dose (solution or tablets) of valganciclovir starting within 10 days of kidney transplant for up to 200 days post-transplant. Dose \[in milligrams (mg)\] was calculated using the algorithm \[7 \* Body Surface Area \* Creatinine Clearance\].
|
|---|---|
|
Treatment Period
Withdrawal by Subject
|
1
|
|
Treatment Period
Adverse Event
|
6
|
|
Treatment Period
Patient did not receive study drug
|
1
|
Baseline Characteristics
A Study of Oral Valcyte (Valganciclovir) in Pediatric Kidney Transplant Recipients
Baseline characteristics by cohort
| Measure |
Valganciclovir
n=56 Participants
Participants received a once daily oral dose (solution or tablets) of valganciclovir starting within 10 days of kidney transplant for up to 200 days post-transplant. Dose (in mg) was calculated using the algorithm \[7 \* Body Surface Area \* Creatinine Clearance\].
|
|---|---|
|
Age, Customized
≤ 2 Years
|
6 Participants
0.5 • n=5 Participants
|
|
Age, Customized
> 2 to < 12 Years
|
18 Participants
2.5 • n=5 Participants
|
|
Age, Customized
≥ 12 Years
|
32 Participants
1.3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
25 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
31 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 52 weeksPopulation: Safety Population included all enrolled patients who received at least one dose of study medication and had at least one post-baseline assessment of safety.
An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. Pre-existing conditions which worsen during a study were reported as AEs. A SAE was any experience that: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically significant.
Outcome measures
| Measure |
Valganciclovir
n=56 Participants
Participants received a once daily oral dose (solution or tablets) of valganciclovir starting within 10 days of kidney transplant for up to 200 days post-transplant. Dose (in mg) was calculated using the algorithm \[7 \* Body Surface Area \* Creatinine Clearance\].
|
|---|---|
|
Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) or Withdrawal Due to AEs
Adverse Events
|
56 Participants
|
|
Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) or Withdrawal Due to AEs
Serious Adverse Events
|
41 Participants
|
|
Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) or Withdrawal Due to AEs
Withdrawals due to AE
|
6 Participants
|
SECONDARY outcome
Timeframe: 52 weeksPopulation: Intent-to-treat (ITT) population included all enrolled patients who had taken at least one dose of study medication.
A polymerase chain reaction (PCR) based assay or antigenaemia assay was used for the qualitative assessment of CMV viremia (presence of CMV in the blood) by each study center as part of the clinical assessment required for diagnosis of CMV infection.
Outcome measures
| Measure |
Valganciclovir
n=56 Participants
Participants received a once daily oral dose (solution or tablets) of valganciclovir starting within 10 days of kidney transplant for up to 200 days post-transplant. Dose (in mg) was calculated using the algorithm \[7 \* Body Surface Area \* Creatinine Clearance\].
|
|---|---|
|
Number of Participants With Cytomegalovirus (CMV) Infection in the First 52 Weeks Post-Transplant as Assessed by the Investigator
|
3 Participants
|
SECONDARY outcome
Timeframe: 52 weeksPopulation: Intent-to-treat (ITT) population included all enrolled patients who had taken at least one dose of study medication.
A polymerase chain reaction (PCR) based assay or antigenaemia assay was used for the qualitative assessment of CMV viremia by each study center as part of the clinical assessment required for diagnosis of CMV infection. CMV disease included CMV syndrome or tissue invasive CMV. CMV syndrome required fever ≥ 38 degrees Celsius, severe malaise, leukopenia on 2 separate measurements, atypical lymphocytosis ≥ 5%, thrombocytopenia, elevation of hepatic transaminases and presence of CMV in blood. Tissue Invasive CMV required evidence of localized CMV infection in a biopsy or other appropriate symptom and relevant symptoms or signs of organ dysfunction.
Outcome measures
| Measure |
Valganciclovir
n=56 Participants
Participants received a once daily oral dose (solution or tablets) of valganciclovir starting within 10 days of kidney transplant for up to 200 days post-transplant. Dose (in mg) was calculated using the algorithm \[7 \* Body Surface Area \* Creatinine Clearance\].
|
|---|---|
|
Number of Participants With Cytomegalovirus (CMV) Disease in the First 52 Weeks Post-Transplant as Assessed by the Investigator
Tissue Invasive CMV
|
0 Participants
|
|
Number of Participants With Cytomegalovirus (CMV) Disease in the First 52 Weeks Post-Transplant as Assessed by the Investigator
CMV Syndrome
|
1 Participants
|
SECONDARY outcome
Timeframe: 52 weeksPopulation: ITT population included all enrolled patients who had taken at least one dose of study medication.
Blood samples were sent to a central lab for the quantitative assessment of CMV viral load (amount of CMV in the blood) by an FDA-approved molecular-based assay. The number of participants in each category is reported in copies/milliliter (CP/mL). CMV DNA is detected in all categories \< 150 CP/mL and above.
Outcome measures
| Measure |
Valganciclovir
n=56 Participants
Participants received a once daily oral dose (solution or tablets) of valganciclovir starting within 10 days of kidney transplant for up to 200 days post-transplant. Dose (in mg) was calculated using the algorithm \[7 \* Body Surface Area \* Creatinine Clearance\].
|
|---|---|
|
Number of Participants With Peak Cytomegalovirus (CMV) Viral Load up to Week 52 Post-Transplant
> 5,000 CP/mL
|
1 Participants
|
|
Number of Participants With Peak Cytomegalovirus (CMV) Viral Load up to Week 52 Post-Transplant
No CMV DNA Detected
|
30 Participants
|
|
Number of Participants With Peak Cytomegalovirus (CMV) Viral Load up to Week 52 Post-Transplant
< 150 CP/mL
|
16 Participants
|
|
Number of Participants With Peak Cytomegalovirus (CMV) Viral Load up to Week 52 Post-Transplant
150 to 1,000 CP/mL
|
6 Participants
|
|
Number of Participants With Peak Cytomegalovirus (CMV) Viral Load up to Week 52 Post-Transplant
1,001 to 5,000 CP/mL
|
3 Participants
|
SECONDARY outcome
Timeframe: 52 WeeksPopulation: ITT population included all enrolled patients who had taken at least one dose of study medication.
Renal biopsies were performed as medically indicated. Biopsies were assessed histologically using the updated Banff criteria 1997.
Outcome measures
| Measure |
Valganciclovir
n=56 Participants
Participants received a once daily oral dose (solution or tablets) of valganciclovir starting within 10 days of kidney transplant for up to 200 days post-transplant. Dose (in mg) was calculated using the algorithm \[7 \* Body Surface Area \* Creatinine Clearance\].
|
|---|---|
|
Number of Participants With Biopsy Proven Rejection
≤ 2 Years
|
1 Participants
|
|
Number of Participants With Biopsy Proven Rejection
>2 to <12 Years
|
1 Participants
|
|
Number of Participants With Biopsy Proven Rejection
≥ 12 Years
|
3 Participants
|
SECONDARY outcome
Timeframe: 52 WeeksPopulation: ITT population included all enrolled patients who had taken at least one dose of study medication.
Graft loss was defined as the institution of chronic dialysis (at least 6 consecutive weeks), transplant nephrectomy, or retransplantation.
Outcome measures
| Measure |
Valganciclovir
n=56 Participants
Participants received a once daily oral dose (solution or tablets) of valganciclovir starting within 10 days of kidney transplant for up to 200 days post-transplant. Dose (in mg) was calculated using the algorithm \[7 \* Body Surface Area \* Creatinine Clearance\].
|
|---|---|
|
Number of Participants With Graft Loss
|
0 Participants
|
SECONDARY outcome
Timeframe: 52 WeeksPopulation: ITT population included all enrolled patients who had taken at least one dose of study medication.
Outcome measures
| Measure |
Valganciclovir
n=56 Participants
Participants received a once daily oral dose (solution or tablets) of valganciclovir starting within 10 days of kidney transplant for up to 200 days post-transplant. Dose (in mg) was calculated using the algorithm \[7 \* Body Surface Area \* Creatinine Clearance\].
|
|---|---|
|
Number of Participants With Death
|
0 Participants
|
SECONDARY outcome
Timeframe: 52 WeeksPopulation: All patients meeting the resistance analysis criteria are included into the resistance analysis.
All patients with measurable CMV had both UL54 and UL97 genes sequenced to assess for known CMV resistance to ganciclovir.
Outcome measures
| Measure |
Valganciclovir
n=10 Participants
Participants received a once daily oral dose (solution or tablets) of valganciclovir starting within 10 days of kidney transplant for up to 200 days post-transplant. Dose (in mg) was calculated using the algorithm \[7 \* Body Surface Area \* Creatinine Clearance\].
|
|---|---|
|
Number of Participants With Known Ganciclovir Resistance (Mutations in Either UL54 or UL97 Genes)
UL54
|
0 Participants
|
|
Number of Participants With Known Ganciclovir Resistance (Mutations in Either UL54 or UL97 Genes)
UL97
|
1 Participants
|
Adverse Events
Valganciclovir
Serious adverse events
| Measure |
Valganciclovir
n=56 participants at risk
Participants received a once daily oral dose (solution or tablets) of valganciclovir starting within 10 days of kidney transplant for up to 200 days post-transplant. Dose (in mg) was calculated using the algorithm \[7 \* Body Surface Area \* Creatinine Clearance\].
|
|---|---|
|
Infections and infestations
Urinary Tract Infection
|
12.5%
7/56
|
|
Infections and infestations
Escherichia Urinary Tract Infection
|
8.9%
5/56
|
|
Infections and infestations
Gastroenteritis
|
7.1%
4/56
|
|
Infections and infestations
Viral Upper Respiratory Tract Infection
|
5.4%
3/56
|
|
Infections and infestations
Bacterial Pyelonephritis
|
3.6%
2/56
|
|
Infections and infestations
Peritonitis
|
3.6%
2/56
|
|
Infections and infestations
Pyelonephritis
|
3.6%
2/56
|
|
Infections and infestations
Viral Infection
|
3.6%
2/56
|
|
Infections and infestations
Chronic Sinusitis
|
1.8%
1/56
|
|
Infections and infestations
Diarrhoea Infectious
|
1.8%
1/56
|
|
Infections and infestations
Gastroenteritis Norovirus
|
1.8%
1/56
|
|
Infections and infestations
Gastrointestinal Protozoal Infection
|
1.8%
1/56
|
|
Infections and infestations
Gastrointestinal Viral Infection
|
1.8%
1/56
|
|
Infections and infestations
Infection
|
1.8%
1/56
|
|
Infections and infestations
Pneumonia Mycoplasmal
|
1.8%
1/56
|
|
Infections and infestations
Pneumonia Respiratory Syncytial Viral
|
1.8%
1/56
|
|
Infections and infestations
Pyelonephritis Acute
|
1.8%
1/56
|
|
Infections and infestations
Rotavirus Infection
|
1.8%
1/56
|
|
Infections and infestations
Septic Shock
|
1.8%
1/56
|
|
Infections and infestations
Urinary Tract Infection Bacterial
|
1.8%
1/56
|
|
Infections and infestations
Urosepsis
|
1.8%
1/56
|
|
Infections and infestations
Varicella
|
1.8%
1/56
|
|
Blood and lymphatic system disorders
Neutropenia
|
8.9%
5/56
|
|
Blood and lymphatic system disorders
Leukopenia
|
3.6%
2/56
|
|
Blood and lymphatic system disorders
Pancytopenia
|
3.6%
2/56
|
|
Blood and lymphatic system disorders
Anaemia
|
1.8%
1/56
|
|
Blood and lymphatic system disorders
Bicytopenia
|
1.8%
1/56
|
|
Renal and urinary disorders
Bladder Dysfunction
|
1.8%
1/56
|
|
Renal and urinary disorders
Neurogenic Bladder
|
1.8%
1/56
|
|
Renal and urinary disorders
Proteinuria
|
1.8%
1/56
|
|
Renal and urinary disorders
Ureteric Obstruction
|
1.8%
1/56
|
|
Renal and urinary disorders
Urethral Obstruction
|
1.8%
1/56
|
|
Renal and urinary disorders
Urinary Tract Obstruction
|
1.8%
1/56
|
|
Renal and urinary disorders
Vesicoureteric Reflux
|
1.8%
1/56
|
|
Investigations
Blood Creatinine Increased
|
8.9%
5/56
|
|
Investigations
HLA Marker Study Positive
|
1.8%
1/56
|
|
Immune system disorders
Transplant Rejection
|
5.4%
3/56
|
|
Immune system disorders
Kidney Transplant Rejection
|
1.8%
1/56
|
|
Metabolism and nutrition disorders
Dehydration
|
3.6%
2/56
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
1.8%
1/56
|
|
Metabolism and nutrition disorders
Type 1 Diabetes Mellitus
|
1.8%
1/56
|
|
Gastrointestinal disorders
Abdominal Pain
|
1.8%
1/56
|
|
Gastrointestinal disorders
Aphthous Stomatitis
|
1.8%
1/56
|
|
Gastrointestinal disorders
Nausea
|
1.8%
1/56
|
|
Gastrointestinal disorders
Vomiting
|
1.8%
1/56
|
|
Injury, poisoning and procedural complications
Complications Of Transplant Surgery
|
1.8%
1/56
|
|
Injury, poisoning and procedural complications
Complications Of Transplanted Kidney
|
1.8%
1/56
|
|
Nervous system disorders
Benign Intracranial Hypertension
|
1.8%
1/56
|
|
Nervous system disorders
Convulsion
|
1.8%
1/56
|
|
Nervous system disorders
Headache
|
1.8%
1/56
|
|
Eye disorders
Papilloedema
|
1.8%
1/56
|
|
General disorders
Device Leakage
|
1.8%
1/56
|
|
Respiratory, thoracic and mediastinal disorders
Tonsillar Hypertrophy
|
1.8%
1/56
|
|
Surgical and medical procedures
Vesicoureteral Reflux Surgery
|
1.8%
1/56
|
|
Vascular disorders
Hypertension
|
1.8%
1/56
|
Other adverse events
| Measure |
Valganciclovir
n=56 participants at risk
Participants received a once daily oral dose (solution or tablets) of valganciclovir starting within 10 days of kidney transplant for up to 200 days post-transplant. Dose (in mg) was calculated using the algorithm \[7 \* Body Surface Area \* Creatinine Clearance\].
|
|---|---|
|
Infections and infestations
Upper respiratory tract infection
|
35.7%
20/56
|
|
Infections and infestations
Urinary tract infection
|
23.2%
13/56
|
|
Infections and infestations
Nasopharyngitis
|
10.7%
6/56
|
|
Infections and infestations
BK virus infection
|
8.9%
5/56
|
|
Infections and infestations
Pharyngitis
|
7.1%
4/56
|
|
Infections and infestations
Escherichia urinary tract infection
|
5.4%
3/56
|
|
Infections and infestations
Gastroenteritis
|
5.4%
3/56
|
|
Blood and lymphatic system disorders
Leukopenia
|
21.4%
12/56
|
|
Blood and lymphatic system disorders
Neutropenia
|
21.4%
12/56
|
|
Blood and lymphatic system disorders
Anaemia
|
17.9%
10/56
|
|
Gastrointestinal disorders
Diarrhoea
|
32.1%
18/56
|
|
Gastrointestinal disorders
Abdominal pain
|
16.1%
9/56
|
|
Gastrointestinal disorders
Vomiting
|
10.7%
6/56
|
|
Gastrointestinal disorders
Abdominal pain upper
|
7.1%
4/56
|
|
Gastrointestinal disorders
Nausea
|
7.1%
4/56
|
|
Gastrointestinal disorders
Constipation
|
5.4%
3/56
|
|
Nervous system disorders
Headache
|
21.4%
12/56
|
|
Nervous system disorders
Tremor
|
17.9%
10/56
|
|
Nervous system disorders
Dizziness
|
5.4%
3/56
|
|
Renal and urinary disorders
Dysuria
|
17.9%
10/56
|
|
Renal and urinary disorders
Haematuria
|
10.7%
6/56
|
|
Renal and urinary disorders
Renal tubular acidosis
|
8.9%
5/56
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
7.1%
4/56
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
7.1%
4/56
|
|
Metabolism and nutrition disorders
Metabolic acidosis
|
5.4%
3/56
|
|
Investigations
Blood creatinine increased
|
12.5%
7/56
|
|
Investigations
Weight increased
|
7.1%
4/56
|
|
General disorders
Pyrexia
|
16.1%
9/56
|
|
General disorders
Oedema peripheral
|
5.4%
3/56
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
10.7%
6/56
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
5.4%
3/56
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
5.4%
3/56
|
|
Vascular disorders
Hypertension
|
14.3%
8/56
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
7.1%
4/56
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.4%
3/56
|
|
Skin and subcutaneous tissue disorders
Acne
|
5.4%
3/56
|
|
Psychiatric disorders
Insomnia
|
5.4%
3/56
|
Additional Information
Medical Communications
Hoffman-LaRoche
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER